COMPARISON OF THE POTENTIATING EFFECTS OF NICORANDIL AND ITS DENITRATED METABOLITE (SG-86) ON THE ADENOSINE-INDUCED VASODEPRESSION IN RATS

The potentiating activity of SG-86[N-(2-hydroxyethyl)nicotinamide], a denitrated metabolite of nicorandil, on the adenosine-induced vasodepr ession was compared with that of nicorandil in anesthetized rats. Sing le bolus iv adenosine (3-100 mu g/kg) produced dose-dependent reductio ns of blood pressure, accompanied by slight decreases (except for 100 mu g/kg) in heart rate. The adenosine-induced vasodepression was signi ficantly enhanced during iv infusion of either SG-86 (100 mu g/kg per min) as well as nicorandil (10 mu g/kg per min). The enhancement of ad enosine action by them did not occur in the presence of glibenclamide (20 mg/kg iv). Single bolus iv injections of SG-86 (0.3-30 mg/kg), exc ept for 30 mg/kg, which caused a glibenclamide-sensitive decrease by a bout 5-10 mm Hg in mean arterial blood pressure, had no effects on blo od pressure and heart rate, whereas those of nicorandil (30-300 mu g/k g) elicited overt reduction of blood pressure, accompanied by decrease s in heart rate. The present results revealed that SG-86, like nicoran dil, significantly enhanced the vasodepressor response to adenosine, p robably in part through K-ATP channel activation, and that the activit y of SG-86 was about 10 times less potent than that of nicorandil. (C) Elsevier, Paris.